Interval Training Normalizes Cardiomyocyte Function, Diastolic Ca <sup>2+</sup> Control, and SR Ca <sup>2+</sup> Release Synchronicity in a Mouse Model of Diabetic Cardiomyopathy
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- Tomas O. Stølen
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Morten Andre Høydal
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Ole Johan Kemi
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Daniele Catalucci
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Marcello Ceci
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Ellen Aasum
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Terje Larsen
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Natale Rolim
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Gianluigi Condorelli
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Godfrey L. Smith
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
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- Ulrik Wisløff
- From the Department of Circulation and Medical Imaging (T.O.S., M.A.H., N.R., G.L.S., U.W.), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs University Hospital (T.O.S., M.A.H., U.W.), Trondheim, Norway; the Institute of Biomedical and Life Sciences (O.J.K., G.L.S.), University of Glasgow, UK; the Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica (D.C., M.C., G.C.), Scientific and Technology Pole, Milan, Italy; the Istituto Tecnologie Biomediche (ITB) -...
説明
<jats:p> <jats:bold> <jats:italic>Rationale:</jats:italic> </jats:bold> In the present study we explored the mechanisms behind excitation–contraction (EC) coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db). </jats:p> <jats:p> <jats:bold> <jats:italic>Objective:</jats:italic> </jats:bold> We determined whether 13 weeks of aerobic interval training could restore cardiomyocyte Ca <jats:sup>2+</jats:sup> cycling and EC coupling. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results:</jats:italic> </jats:bold> Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca <jats:sup>2+</jats:sup> leak, reduced synchrony of Ca <jats:sup>2+</jats:sup> release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca <jats:sup>2+</jats:sup> and caffeine-induced Ca <jats:sup>2+</jats:sup> release. Additionally, the rate of SR Ca <jats:sup>2+</jats:sup> ATPase–mediated Ca <jats:sup>2+</jats:sup> uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca <jats:sup>2+</jats:sup> release indicated increased Na <jats:sup>+</jats:sup> /Ca <jats:sup>2+</jats:sup> -exchanger activity. The increased SR-Ca <jats:sup>2+</jats:sup> leak was attributed to increased Ca <jats:sup>2+</jats:sup> -calmodulin–dependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca <jats:sup>2+</jats:sup> leak on inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca <jats:sup>2+</jats:sup> release synchronicity, T-tubule density, twitch Ca <jats:sup>2+</jats:sup> amplitude, SR Ca <jats:sup>2+</jats:sup> ATPase and Na <jats:sup>+</jats:sup> /Ca <jats:sup>2+</jats:sup> -exchanger activities, and SR-Ca <jats:sup>2+</jats:sup> leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca <jats:sup>2+</jats:sup> handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca <jats:sup>2+</jats:sup> load when compared with the sedentary db/db mice. EC coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training–induced effects are not via normalization of the diabetic condition. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions:</jats:italic> </jats:bold> These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type. </jats:p>
収録刊行物
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- Circulation Research
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Circulation Research 105 (6), 527-536, 2009-09-11
Ovid Technologies (Wolters Kluwer Health)
